Broad objectives will be to better define the role which group B coxsackieviruses may play in chronic heart disease, diabetes and polymyositis, and to determine the extent to which particular antigenic determinants can be associated with the ability of virus strains to persist in the host or to display certain tissue tropisms or pathological features. The ability of group B coxsackieviruses to establish persistent infections in a mouse model will be explored using more sensitive and specific methods than those employed in the past, and the effect of variables in the host and virus on persistence of infection will be studied. Monoclonal antibodies will be produced in hybridomas derived by fusing spleen cells from coxsackievirus-immunized mice with cells of a mouse myeloma line, and monospecific antisera will be prepared by cross-absorption of standard antisera. These will be used, together with highly discriminating procedures including kinetic neutralization, competition radioimmunoassay and immune precipitation, to detect unique antigens associated with certain pathological features of coxsackieviruses. If unique antigens can be associated with diabetogenic or myocarditic virus strains, antibodies to these antigens will be sought in patients with diabetes or heart disease. Field strains of group B coxsackieviruses isolated over the past 20 years will be examined for antigenic drift and for diabetogenic, myocarditic and myositic properties. Antigen demonstrable in heart tissue of mice infected with myocarditic strains of coxsackieviruses will be studied from the standpoint of persistence in the host, immune response to the antigen, and relationship of the antigen to structural viral proteins.